Our objective is to understand how the intrinsic electrical properties of a neuron operate upon various synaptic input waveforms to produce the neuron's output. Since most CNS neurons utilize nerve impulses to communicate between their input synapses and the output synapses which are located at the end of a long axon, our studies focus upon how this impulse train is produced at the beginning of the axon. During low levels of input activity, the occasional excursions through threshold produce impulses which are temporally correlated with activity in upstream neurons. When there is a steady suprathreshold level of input activity, pacemaker-like rhythmic impulse production occurs; we seek to understand the oscillator mechanisms which control the rate of this rhythmic discharge. Most of our efforts presently focus upon a mode of repetitive firing where "extra impulses" appear superimposed upon the pacemaker-like activity; these extra impulses augment the sensitivity in certain regions of the neuronal input-output curve and sometimes produce negative sensitivity regions. The extra impulses also produce a prominent clustering in the impulse train; this patterning is often suspected of carrying a special message to downstream neurons. Our experimental studies of cat motor cortex neurons, lobster stretch receptors, cat dorsal root ganglia and demyelinated axons explore the way in which the neuron shape influences both rhythmic and extra impulse production. In addition to using computer simulations to model such experimental data, we will use simulations to explore the consequences of segmental demyelination, of the unusual neuron shapes seen in human mental retardation, and of the anatomical pathology seen in trigeminal neuralgias. As in our identification of augmented extra impulse production in epileptic cerebral cortex, we can assist in the identification of pathophysiological mechanisms using simple extracellular spontaneous activity recordings from various disease states.